Mutant AIEC Found to be Protective in Colitis in Mice

By Lynn McCain | 23 November

The Department of Pathology’s Dr. Naohiro Inohara with Drs. Mizuho Hasegawa, Gabriel Nuñez, and colleagues, recently published important findings in PLoS Pathogens that may lead to strategies for the treatment and prevention of colitis. Susceptibility to colitis is associated with abnormal changes in microbial populations of the gut in individuals with impaired immune systems. A common change is the increased abundance of adherent-invasive Escherichia coli (AIEC), a bacterial population that is associated with the development of inflammatory bowel disease. However, the precise mechanisms by which AIEC influences colitis remain poorly understood.

In this study, Inohara et al. show that changes in the microbial population induced by administration of antibiotics include a bloom of Escherichia coli, which was associated with worsening chemically-induced colitis in IL-22-deficient mice. Ecoli strains isolated from the gut of such mice exhibited AIEC features, high ability to outcompete related bacteria and resistance to the host complement system in vitro. Mutation of the gene required for the biosynthesis of lipopolysaccharide O side chains rendered AIEC sensitive to complement-mediated elimination in colitic mice. Upon oral inoculation, the mutant AIEC protected the mice from colitis. This study provides new insights into the mechanisms by which gut microbes control colitis via the complement system and a possible strategy for the generation of probiotic strains resistant to host elimination.

Click here to read more about this important finding.

 
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